Left atrial appendage occlusive devices

ABSTRACT

An occlusive device for left atrial appendage occlusion that has a membrane component configured to inhibit passage of blood and an expandable frame formed from a plurality of wires having a cupped occlusive component at least partially covered with the membrane component, one or more anchors with looped ends and a hub component. The occlusive device can be delivered percutaneously. The occlusive device is useful in the occlusion of the left atrial appendage.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional PatentApplication Ser. No. 61/413,253 filed Nov. 12, 2010; U.S. Ser. No.61/413,649 filed Nov. 15, 2010; and U.S. Ser. No. 61/535,888 filed Sep.16, 2011, each of which is incorporated by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to occlusive devices useful, for example,in occluding structures or conduits within a patient, particularly anatrial appendage in the human heart. Devices of the present inventioncan be delivered percutaneously or in an endovascular fashion.

BACKGROUND OF THE INVENTION

Embolic stroke is the nation's third leading killer, and is a majorcause of disability. There are over 780,000 strokes per year in theUnited States alone. Of these, roughly 110,000 are hemorrhagic, and670,000 are ischemic (either due to vessel narrowing or to embolism).The most common cause of ischemic stroke of cardiac origin isthromboemboli due to atrial fibrillation. One out of every six strokes(approximately 130,000 per year) is attributed to atrial fibrillation.Atrial fibrillation is the most common heart arrhythmia; it results in arapid and chaotic heartbeat that lowers cardiac output and leads toirregular and turbulent blood flow in the vascular system. There areover eight million people worldwide with atrial fibrillation, with abouteight hundred thousand new cases reported each year. Atrial fibrillationis associated with a 500 percent greater risk of stroke compared withage-matched healthy controls. A patient with atrial fibrillationtypically has a significantly decreased quality of life due, in part, tothe fear of stroke, and the pharmaceutical regimen necessary to reducethat risk.

When patients develop atrial thrombus from atrial fibrillation, the clotoccurs in or originates from the left atrial appendage (LAA) of theheart over ninety percent of the time. The left atrial appendage is aclosed cavity which looks like a small thumb or windsock; it isconnected to the anterolateral wall of the left atrium between themitral valve and the root of the left pulmonary vein. The left atrialappendage contracts with the left atrium during a normal heart cycle,thus keeping blood from becoming stagnant. However, with atrialfibrillation, the left atrial appendage often fails to contract with anyvigor due to the disorganized electrical signals. As a result, thrombusformation is predisposed to form in the stagnant blood within the leftatrial appendage.

Pharmacological therapies for stroke prevention in atrial fibrillationpatients such as oral or systemic administration of warfarin have oftenbeen inadequate due to serious side effects and lack of patientcompliance. Invasive surgical or thorascopic techniques have been usedto obliterate the left atrial appendage, however, many patients are notsuitable candidates for such procedures due to compromised condition orprevious cardiac surgery. In addition, the perceived risks of thesesurgical procedures often outweigh the potential benefits.

Many of the current commercial devices that attempt to occlude the leftatrial appendage for stroke prevention in atrial fibrillation patientsutilize a rigid, cylindrical support frame with tissue-piercing fixationmembers and macroporous filtering membranes that allow the passage ofblood. These devices have a number of issues and/or potential drawbacks.The opening (ostium) of the left atrial appendage varies in geometry andsize. Sealing the left atrial appendage with a rigid frame thatpresupposes a circular ostium can be less effective at preventingthromboemboli from entering systemic circulation.

Securing a device in the left atrial appendage is a major safety concernto physicians. Many of the current left atrial appendage occlusion orfiltering devices employ tissue-piercing fixation members. The tissue ofthe left atrial appendage is generally fragile and thin. The heart isencased in a tough, non-elastic pericardial sac. This makes bleedingfrom the heart through the holes caused by the tissue-piercing fixationmembers into the pericardial space a potentially life-threateningsituation due to the potential for tamponade (compression of the heartwhen blood or fluid builds up in the space between the myocardium (heartmuscle) and the pericardium (outer covering sac of the heart)).

Another concern with many of the current devices is the filtering typemembranes. These membranes are macroporous and do not provide immediatecessation of blood flow through the membrane. Such membranes can takehours to weeks to substantially occlude. The possibility exists forthromboemboli to enter the blood stream while the clotting/occludingprocess of the filtering membrane takes place. Many of these atrialfibrillation patients are on some type of blood thinning (anticoagulantor antiplatelet) medication, which could prolong the clotting/occludingprocess for these filtering membranes and expose patients to strokerisk.

SUMMARY OF THE INVENTION

Occlusive devices have been discovered comprising a membrane componentconfigured to inhibit passage of blood and an expandable frame formedfrom a plurality of wires having a cupped occlusive component at leastpartially covered with the membrane component, one or more anchors withlooped ends and a hub component.

Some embodiments of an occlusive device of the present inventioncomprise a membrane component configured to inhibit passage of blood;and an expandable frame having a distal end and a proximal end andhaving: a cupped occlusive component, one or more anchors, and a hubcomponent between said occlusive component and said one or more anchors.In some embodiments the cupped occlusive component is at least partiallycovered by said membrane component. In some embodiments one or more ofthe anchors has a looped end. In some embodiments the expandable frameis formed from a plurality of wires extending from a proximal end to adistal end of said frame.

Some embodiments comprise an occlusive device comprising a proximalportion, having a membrane component configured to inhibit passage ofblood and an expandable frame formed from a plurality of wires having acupped occlusive component at least partially covered with the membranecomponent, connected by at least one flexible connector to a distalportion having one or more anchors.

Some embodiments comprise a membrane component configured to inhibitpassage of blood; and an expandable frame having a distal end and aproximal end and having: a cupped occlusive component having a firstconfiguration upon application of tensile force and a secondconfiguration upon release of said tensile force, one or more anchors,and a hub component between said occlusive component and said one ormore anchors. In some embodiments the cupped occlusive component is atleast partially covered by said membrane component. In some embodimentsthe configuration of the cupped occlusive component is a tube. In someembodiments the second configuration is a cupped shape formed from atleast two overlapping petals configured to allow movement between the atleast two overlapping petals. In some embodiments the expandable frameis formed from a plurality of wires extending from a proximal end to adistal end of said frame.

Other advantages, benefits and novel features of the embodiments of thepresent invention will become apparent from the following detaileddescription and accompanying drawings. All references, publications andpatents, including the figures and drawings included therewith, areincorporated by reference in their entirety.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an embodiment of the device.

FIG. 2 provides a perspective view of the device of FIG. 1.

FIG. 3 provides an alternate view of the device of FIG. 1.

FIG. 4 provides an end on view of the device of FIG. 1.

FIG. 5A illustrates a feature of an anchor of the device of FIG. 1.

FIG. 5B illustrates an embodiment of an anchor of the device.

FIG. 5C illustrates an embodiment of an anchor of the device.

FIG. 6 illustrates an embodiment of the device.

FIG. 7 illustrates a device placed on a delivery catheter situated in adelivery sheath.

FIG. 8 illustrates an alternate method of placing a device on a deliverycatheter situated in a delivery sheath.

FIG. 9 provides a perspective illustration of an embodiment of thedevice.

FIGS. 10A and 10B illustrate two embodiments of related devices as theywould appear extended on a mandrel.

FIG. 11 illustrates wire forming tooling for manufacturing embodiments.

FIG. 12A shows a cut away view of a heat set tool used in themanufacture of an embodiment of the device.

FIG. 12B provides a perspective of a heat set mandrel used in themanufacture of an embodiment of the device.

FIG. 12C shows an exterior of a heat set tool used in the manufacture ofan embodiment of the device.

FIG. 12D shows a cross bar for utilization with a heat set tool used inthe manufacture of an embodiment of the device.

FIG. 13 shows a perspective view of a mandrel used in the attachment ofthe membrane component manufacture of the device.

FIG. 14 shows a perspective view of a mandrel used in the attachment ofthe membrane component manufacture of the device.

FIGS. 15A-D illustrate a flexible wire connector.

FIGS. 16A-B show a flexible wire connector.

FIGS. 17A-B show a flex joint with a chain link type of connection.

FIGS. 18A-H provide views of types of beaded or flexible connectors.

FIGS. 19A-B show an ePTFE tube flexible connector.

FIGS. 20A-H show various types of flexible connectors.

FIGS. 21A-B show various configurations of threaded cap type of flexibleconnector attachment mechanisms.

FIGS. 22A-C show various configurations of a flexible connector.

FIG. 23 illustrates an embodiment of an anchor.

FIG. 24 illustrates an embodiment of an anchor.

FIG. 25 illustrates an embodiment of an anchor.

FIG. 26 illustrates a cross-section of an embodiment of a keyed eyeletcap.

FIG. 27A shows a perspective view of an embodiment of the device using amodular anchoring component.

FIG. 27B shows an expanded view of a modular anchoring hub component.

DETAILED DESCRIPTION OF THE INVENTION

Despite various efforts in the field, there remains an unmet need forminimally invasive methods and associated devices for cardiovascularocclusion, particularly in the left atrial appendage. The devices of thepresent invention conform to the anatomy of a variety of left atrialappendage ostia, demonstrate firm and secure anchoring with reduced riskof trauma and bleeding from anchoring, and provide rapid cessation ofblood flow across the occluding membrane.

The invention relates to occlusive devices useful in occluding holes,defects, or appendages in the body of a patient, including the heart,such as right or left atrial appendages, fistulas, aneurysms, and patentductus arteriousus, and methods of making and using the same. Theocclusive devices provide a frame that is compliant enough to conform toa wide variety of opening geometries and sizes. Particularly,embodiments of the devices can provide a left atrial appendage occlusiondevice frame that provides firm, secure anchoring with significantlyreduced clinical sequela from piercing or without traumatic piercing ofthe left atrial appendage tissue. Some embodiments provide a membranecomponent configured to inhibit the passage of blood through themembrane, i.e., substantially occludes the flow of blood through themembrane. Some embodiments provide a membrane that is configured toinduce rapid tissue ingrowth and immediately occludes the passage ofblood through the membrane.

Although atrial fibrillation can result in blood clots originating inthe left atrial appendage and the occlusive devices will be illustratedherein with regard to use with the left atrial appendage, the devices ofthe present invention can also be used on the right atrial appendageand, in general, for placement across any aperture of the body,including in the vasculature, where there is a need to prevent bloodclots from escaping or to inhibit or substantially reduce blood flow.

Some embodiments provide a membrane component configured to inhibitpassage of blood and an expandable frame formed from a plurality ofwires having a cupped occlusive component at least partially coveredwith the membrane component, one or more anchors with looped ends, and ahub component. Each of the one or more anchors may have one more orlooped ends, and may further include one or more passive barbs.

In some embodiments, anchors with looped ends are single-leg anchors. Insome embodiments, anchors with looped ends include a first leg and asecond leg, each leg converging at the second end of each leg to form aloop.

FIGS. 1 to 3 are prospective views from three different angles lookingat the device 100 shown in its fully deployed state without anydiametrical constraint (such as it would have when contained within adelivery catheter or, to a lesser extent as it would have within anatrial appendage). FIG. 4 is an end view of device 100 looking into thecupped, concave side of the proximal end of device 100.

Device 100 can be manufactured from multiple individual lengths offlexible, fatigue resistant wire 101 as will be further described. Insome embodiments, the proximal end of device 100 can have a proximaleyelet 114, and a distal eyelet 113 located adjacent the distal end ofdevice 100. A lumen can extend through both eyelets 113 and 114 andthrough the length of device 100. Device 100 also can have an occlusivecomponent 104 located adjacent the proximal end and one or more anchors106 located at the opposing distal end, with the occlusive component 104and one or more anchors 106 separated by hub 110. The occlusivecomponent 104 can comprise multiple petals 112, each petal 112 having anexpandable frame 102 formed from a portion of a length of wire 101. Eachpetal 112 can be covered or substantially covered with a membranecomponent 109 that is supported by expandable frame 102. In someembodiments, a single membrane covering 109 can be used to substantiallycover all multiple petals 112.

In some embodiments one or more anchors 106 and/or barbs 211 contact thewall or body of the left atrial appendage. In some embodiments the pointof contact between the anchors and/or barbs is the endocardial surfacewithin the left atrial appendage. While in some embodiments one or moreanchors and/or barbs penetrate into the endocardial surface of the leftatrial appendage, in some other embodiments, there is no penetration ofthe endocardial surface. In some embodiments, some anchors of the devicepenetrate the endocardial surface while other anchors of the device donot penetrate the endocardial surface. In some embodiments, some barbsof the device penetrate the endocardial surface while other barbs of thedevice do not penetrate the endocardial surface. In some embodiments oneor more anchors contact trabeculation of the endocardial surface.

In some embodiments, one or more anchors 106 are formed from portions ofthe lengths of wires 101. In some embodiments, two or more, three ormore, four or more, five or more, six or more, seven or more, eight ormore, or nine or more anchors stabilize and/or secure the device 100.Further examples of anchors are provided below.

In some embodiments, one or more anchors 106 has a looped end 107 and isprovided with a membrane covering 108 over a portion of the individualanchors 106. FIGS. 1 to 4 show an embodiment of an occlusive device 100.In some embodiments of the device 100, the device is constructed with anexpandable frame 102. The expandable frame comprises the proximal eyelet114 and a distal eyelet 113, the cupped occlusive component, one or moreanchors, and a hub component located between the occlusive component andsaid one or more anchors. The expandable frame 102 can be formed in anysize appropriate for an application. Typically the size of a human leftatrial appendage ostium ranges from about 10 to about 32 mm with theaverage being about 21 mm plus or minus about 4 mm. Device sizes can bemanufactured to encompass the entire range of ostium sizes. Expandableframe 102 can be constructed from any number of fatigue resistant wires101. In some embodiments multiple wires, e.g. four, five, six, seven,eight, nine, or more wires are used in the manufacture of the device.The expandable frame 102 is constructed from wires, for example fatigueresistant wires, that have elastic properties. In some embodimentsexpandable frame 102 is constructed of wires that have elasticproperties that allow for expandable frame 102 to be collapsed forcatheter-based delivery or thoracoscopic delivery, and then self-expandto the desired configuration once positioned in a cavity. The elasticwire can be a spring wire, a shape memory alloy wire or a super-elasticalloy wire. Any wire can be used that has biocompatible characteristicsand is strong, flexible, and resilient. The wire can be, for example,nitinol (NiTi), L605 steel, stainless steel, or any other biocompatiblewire. The elastic wire can also be of a drawn-filled type of nitinolcontaining a different metal at the core. The super-elastic propertiesof nitinol make it a useful material for this application. Nitinol wirecan be heat set into a desired shape. Stainless steel wire is analternative material. It can be plastically deformed into a desiredshape. Wire that is formed to have varying diameters with a centerlessgrind technique can also be used. Other shape memory or plasticallydeformable materials can be suitable in this application.

In some embodiments, expandable frame 102 can be constructed of adrawn-filled type of NiTi wire containing a radiopaque metal such asplatinum at the center. Upon deployment, the wire structure resumes itsdeployed shape without permanent deformation.

Expandable frame 102 and other embodiments of the expandable frames canbe formed from elastic wire materials that have outer diameters (OD)between about 0.12 and about 0.4 mm. Other embodiments can be formedfrom wires with OD of from about 0.2 to about 0.3 mm.

As used herein, the term “about” means a value falling with the rangeencompassed by +/−5% or +/−10% of given value.

When formed, expandable frame 102 comprises a proximal eyelet 114, adistal eyelet 113, a cupped occlusive component 104, a hub component 110and anchor elements 106. The cupped occlusive component 104 is designedto effectively seal or occlude the left atrial appendage. “Cupped”, asused herein, means the occlusive component 104, as seen when device 100is deployed without constraint, is non-planar. The cupped shape of theocclusive component 104 is configured to enhance sealing around theedges of the ostium of the left atrial appendage and apposition to thelateral wall of the left atrium of the heart. The cupped occlusivecomponent 104 has a concave or convex configuration that allowsversatility in device sizing as well as promotes self-centering of thedevice in the left atrial appendage ostium. An occlusive component 104with a concave configuration is shown in FIGS. 1 to 4. An occlusivecomponent 104 with a convex configuration is shown in FIG. 6.

The occlusive component 104 comprises multiple petals 112, i.e. at leasttwo petals, and in some embodiments five petals or more. In someembodiments the multiple petals are present in the occlusive componentin odd numbers. The occlusive component 104 comprises multiple petals112 that are spaced uniformly apart. In some embodiments the multiplepetals 112 are spaced uniformly apart, i.e. the apex of each petal 112is equally spaced about the circumference of the occlusive component104. In some embodiments, the individual petals move independently fromone another within the restraint of the membrane component. Constructingcupped occlusive element 104 of multiple petals 112 increases theconformability of the device to non-circular orifices, which providesfor more effective tissue apposition and sealing. The multiple petals112 also increase the uniformity of the radial force exerted on bodytissues, which provides added safety.

The pre-set elastic wire configuration of expandable frame 102 allowsthe frame to twist during deployment. This twist forms petals 112.Deployed petals 112 form the outer diameter 120 of the expandable frame102. Deployed petals 112, when covered with membrane component 109, formthe cupped occlusive element 104. In some embodiments petals 112 areformed to have overlapping zones to improve sealing qualities. Theradius and shape of petals 112 can be optimized to minimize sharp bendangles in the elastic wire and to minimize unsupported sections ofpetals 112 to improve sealing qualities of the device, reduce bendingfatigue in the wire and aid in reducing device loading forces.

In an embodiment as described in Example 1, during the construction ofthe device, the longest distance between the center pin 22 and the outersurface of the petal jig 38 (illustrated in FIG. 11) establishes theradius of the occlusive component. While in some embodiments there arefive petals, however, in some embodiments there are two, three, four,six, seven, or eight or more petals. In some embodiments at least one ofthe petals is covered with a membrane component 109 to inhibit thepassage of blood through the petals. In some embodiments, each of thepetals is at least partially covered with a membrane component. In someembodiments each of the petals is fully covered with a membranecomponent. Proper positioning and seating of the device is facilitatedby the cupped occlusive element 104 and inhibits blood flow through oraround the device.

Some embodiments of the device are constructed using multiple wires thatextend the full length of the device, thereby resulting in a one-pieceexpandable frame. Alternatively, a multiple-piece embodiment of thedevice can be constructed by joining a proximal portion to a distalportion at the hub 110, e.g. a two-piece device. In creating a two-piececonstruction, the proximal portion and the distal portion can beconnected in a variety of ways. The proximal portion can comprise anocclusive component, a proximal eyelet and, optionally, a hub. Thedistal portion can comprise one or more anchors, a distal eyelet, andoptionally a hub component. The proximal portion and the distal portioncan be joined, for example, with the use of a fluorinated ethylenepropylene (FEP) coated expanded polytetrafluoroethylene (ePTFE) filmwrapped to join the two parts together and subsequently heated to createa durable bond. In some embodiments, the pieces are joined by aconcentric fit, in which one piece is screwed or press fit into theother. In some embodiments two piece construction is utilized whereineach of the pieces is created with different wire types or diameters.For example, in some embodiments the device can be tailored to have ananchor element that is stiffer than the occlusive element. That is, thedistal portion can be constructed with a stiffer (e.g., larger diameter)wire than what is used to create the proximal portion.

The proximal portion and distal portion can also be connected with aflexible connector region 124 between the two elements. In suchembodiments, a proximal portion has a membrane component configured toinhibit passage of blood and an expandable frame formed from a pluralityof wires having a cupped occlusive component 104 at least partiallycovered with the membrane component, connected by at least one flexibleconnector and/or a hub to a distal portion having one or more anchors106. Such connectors can include hinges, springs, and joints.

In some embodiments the flexible connector region 124 is located at orbelow the hub 110. In some embodiments, the connector component isconstructed by winding the wires between the proximal portion and thedistal portion into a spring-like configuration. The spring-likeconfiguration can be formed by winding the wires to form an eyelet 142at the distal portion of the cupped occlusive element 104 and an eyelet144 at the proximal portion of the anchor component 106 with additionalwindings 140 in between the two eyelets 142,144 illustrated in FIG. 15A.

FIG. 15B is a longitudinal cross section that further illustrates aconfiguration with an eyelet at the distal portion of the cuppedocclusive element 142 and an eyelet at the proximal portion of theanchor element 144 separated to show space where flexible connectors canbe inserted. Wires of the additional windings 140 can then be cut out tochange the performance characteristics of the middle spring-likesection. The spring-like center section can also be formed by windingthe wires directly from the cupped occlusive element into the anchorcomponent with no eyelets formed. A spring-like connector can be formedseparately from the cupped occlusive member and the anchor component andbe secured to each by an interference fit either over the eyelet at thedistal portion of the cupped occlusive element 142 and the eyelet at theproximal portion of the anchor element 144 or on the inner diameter ofthe eyelets 142 and 144 as shown in FIGS. 15C and 15D (144 not shown inFIG. 15C). This connection may be enhanced by the addition of a fastenerincluding, for example, glue or adhesive tape.

In some embodiments, a flexible wire connector is formed from the wiresthat form the petals 112 shown in FIG. 16A with articulation arrows 146indicating that the device can be bent along its longitudinal axis. Inthis configuration, the flexible wires continue from the petals 112through the flexible connector region 124 to continue to the anchorcomponents 106. Such a configuration can, in some embodiments, include aconstraint or flexible tube 148 loosely fit around the flexibleconnector region 124, as shown in FIG. 16B. The constraint may beconstructed of any suitable materials as described herein for flexibletubes.

The connector component can, for example be configured of two wire loops126 that form a connection similar to that of a chain link connection asshown in FIGS. 17A and 17B. Wire loops 126 may be secured within theeyelets, for example, by any appropriate adhesive, by welding or by amechanical connection. Alternately or additionally, wire loops 126 maybe formed of one or more of the wires that form the eyelet. The chainlink type of connection may be covered by a flexible sleeve 128(approximate range of motion is indicated by arrows 127) as shown inFIG. 17B, or left uncovered as shown in FIG. 17A. Materials used forsuch a sleeve 128 can be any material with the appropriatebiocompatibility and fatigue performance characteristics such as thoselisted below in relation to a flexible tube connector.

The flexible connector region 124 can be composed of a beaded chain 130connection. The connector component can be a flexible beaded tube 130 asshown in FIG. 18B. As illustrated in FIGS. 18A-18B, 18D-18G, a beadedchain type of connection can be constructed of flexible beaded chain 130or fabricated from a nitinol braid 132. In some embodiments the braidedchain is a composite of a flexible beaded chain 130 and a nitinol braid132. The nitinol braid 132 may be heat set into a “bead” type offormation (135, 136) by inserting into the interior of the braid anynumber of spaced apart ball bearings or other manufacturing aid and thenheat treating the structure. The resulting form simulates that of abeaded chain 132 but would, under tension, have a smaller uniform outerdiameter due to the extension or elongation of the bead form. The beadsresulting from such a treatment can be made of varying sizes 136 asshown in FIGS. 18F-18G.

A coil type of flexible connector 138 as shown in FIG. 18C and FIG. 18Hmay be used as a flexible connector. Such a connector could be formedfrom any suitable material. In some embodiments such a connector isformed of nitinol wire similar to that used to form cupped occlusiveelement 104 and anchors 106. A coil type connector 138 can be configuredto have a diameter and coil pitch mated to the pitch and diameter of theeyelet at the distal portion of the cupped occlusive element 142 and theeyelet at the proximal portion of the anchor element 144 for securing itwithin or on both eyelets 142 and 144. Such a connector 138 could beused as described below to provide tactile feedback and lengthadjustments as shown in FIG. 18H.

In some embodiments the flexible connector is comprised of wires woundinto a tubular, spring-like configuration. Some embodiments include theuse of 2 or more, 4 or more, 6 or more, or 8 or more filars. In someembodiments the filar wires used have an outer diameter of between 0.1mm to about 0.3 mm. In some embodiments, the flexible connector is madefrom flat wire. In some embodiments, the flexible connector is amulti-layer construct including, for example, an inner and outerdiameter layer of flat wire running in opposite pitch directions. Insome embodiments the flexible connector is a construct including flatwire with braiding.

The flexible connectors shown in FIGS. 18A-18H may also be used tochange the length between the eyelet at the distal portion of the cuppedocclusive element 142 and the eyelet at the proximal portion of theanchor element 144. In some embodiments the beaded type of flexiblechain connectors (135, 136) are set at defined and known lengths fromeach other which could provide tactile feedback while adjusting thelength of the middle of the device. Such a system is shown in FIG. 18Gand includes a section of hypotube 131 or other suitably flexiblematerial inserted into the inner diameter of one of the eyelets 142and/or 144 configured to have inner protrusions 133 to provide tactilefeedback during length adjustment. In some embodiments, the device isconfigured so as to permit rotational flexibility and/or lengthadjustability. For example, some embodiments of a device as shown inFIG. 18G allows length adjustability as discrete beads on 130 pass thrua deformable gate 133 as a result of maneuvers performed by theimplanting clinician. In some embodiments length can also be adjustedusing a screw type mechanism where the coils of 138 pass thru thethreads on 144. In some embodiments, a flexible connector permits bothrotational flexibility as well as length adjustability.

The flexible tube can be any suitable polymer. In some embodiments thetube is ePTFE. As shown in FIGS. 19A-19B such a flexible tube made fromePTFE 150 can be connected over the eyelet at the distal portion of thecupped occlusive element 142 and the eyelet at the proximal portion ofthe anchor element 144 (not shown) and secured using various means asdescribed herein. In some embodiments the ePTFE tube has one or moredensified portions. The tube can be a knitted polymer tube, strand orstranded rope. A tube may also be formed from shrink tubing 152 such as,but not limited to, extruded PTFE, reinforced silicone 153 (FIG. 20A) orhelically wrapped PTFE film as illustrated in the longitudinal crosssection FIG. 20B. Reinforcing member 151 can be constructed of anybiocompatible metal such as L605, SST, 316L and the like. The shrinktubing 152 may be adhered to eyelets 142 and 144 by an interference orpressure fit or with any appropriate adhesive. The tube may have bellowssimilar to those in a bending straw. The bellows can be incorporatedinto either a metal tube or a polymer tube. The metal tube 154 can be ahelically wound hollow tube with one or more layers of helically woundfilaments as shown in FIG. 20C-20D. The metal tube 154 can also be a cuthypotube in a variety of patterns shown in FIG. 15E. Such tubes may beconfigured to have a flange 156 at one or both ends to facilitateattachment to the eyelets 142 and 144 of the cupped occlusive member andthe anchor components.

In some embodiments, the flexible connector protrudes through eyelets ofthe occluding disc and the anchoring structure. In some embodiments theflexible connector include caps mounted to the ends of the hypotube. Insome embodiments the caps are welded, permanently affixed (e.g.,superglue, FEP) to the flexible connector. In some embodiments the endcaps prevent movement of device components (i.e. petal supports andanchors) past their respective device end points but allow both movementalong the longitudinal axis of device as well as rotation about thelongitudinal axis of the device. In some embodiments, the flexibleconnector includes internal spacers to prevent components of the distalend of the device from interfering with, rubbing against, or contactingcomponents of the proximal end of the device. In some embodiments, theinternal spacers are a physical spacer or an abraded surface to limitthe extent of movement of components along the device's longitudinalaxis.

In some embodiments, the flexible connector is a hypotube. In someembodiments, the hypotube has an outer diameter from about 0.06″ toabout 0.08″. In some embodiments the hypotube has a wall thickness offrom about 0.1 mm to about 0.2 mm. In some embodiments the hypotube canwithstand a tensile load of 2.2 lbs (10N).

In some embodiments flexible connector 158 is formed of a flexiblematerial such as silicone or urethane as shown in FIG. 20E. Thisconnector can have a clearance fit such that it may be inserted throughthe eyelet at the distal portion of the cupped occlusive element 142 andthe eyelet at the proximal portion of the anchor element 144. It can besecured in place by either use of a formed flange 162 or an attachmentcap 160. In some embodiments the configuration allows rotation of one orboth of the anchor components or the cupped occlusive elementindependent of each other. Silicone can also be used to form anover-mold type of flexible connector 164, as shown in FIG. 20G.Attachment of such a connector at eyelets 142 and 144 may be via atypical over molding process, for example.

An alternate configuration 166 is shown in FIG. 20F. A silicone orurethane molded insert can be inserted and attached in a similar mannerto that described previously. Such an insert may have an increaseddiameter at the flexible joint.

The flexible connector element can also be a universal joint such as theball and socket configuration shown in FIG. 20H. The female socketcomponent 168 may be secured or attached within the eyelet at the distalportion of the cupped occlusive element 142 by any suitable meansdescribed herein. The ball and shaft 170 are fitted within the femalesocket component 168 and the entire universal joint covered by aflexible sleeve 172. The flexible sleeve 172 can be any flexible sleevedescribed herein.

In some embodiments one or more of the flexible connectors can be fixedor attached to eyelets 142 or 144 or both by the use of threaded caps174 and 180 (shown in FIGS. 21A and 21B). One or more of the threadedcaps may be affixed to the flexible tube 178 using a threaded insert 176having, for example, a multi-thread geometry with a matched pitch coilto that of eyelets 142 and 144. Such a configuration can be used forcatheter attachment or device locating or keying. Threaded cap 180 isconfigured similarly to that of threaded cap 174. The threaded insert184 is placed on the inner diameter of eyelets 142 or 144 and a flange182 is used to secure threaded cap 180 to eyelets 142 and 144.

In some embodiments a flexible connector is constructed from acompressed spring. As shown in FIG. 22A, a compressed spring 186 can beconstructed with a clearance fit to allow the spring to be insertedthrough the inner diameter of the eyelets of the device. FIG. 22Adepicts a connector portion shown in cross section to provide clarity.The spring construction can be with a wire or filar diameter and wire orfilar count to achieve the desired flexibility. In this example, thecoil is retained in place with retaining caps 190, which may, in someembodiments, be adhered to the compressed spring with adhesive or with ascrew-type fit. Element 188 is a flexible coupling that can beconstructed of shrink tubing, PTFE film construct, silicone or any othersuitable material. Such a coupling can be constructed with a bellows asdescribed previously. If made from silicone, the flexible coupling 188can optionally be reinforced with metal, such as a wire or stranded wireconstruct. Such wire or reinforcing could be constructed of anybiocompatible metal such as L605, SST, 316L and the like.

As shown in FIGS. 22B and 22C, an alternative configuration to that ofthe compressed spring described above can have a cord or filament 192 inthe place of the compressed spring 186. End caps 190 can be formed withholes to allow the passage and securing of filament 192. Alternatively,as illustrated in FIG. 22C, cord or filament 192 can be threaded throughthe lumens of eyelets 142, 144 and secured, such as by knot 194.

The devices 100 can be delivered in an endovascular fashion through acatheter system comprising a delivery catheter 115 locatedconcentrically within a delivery sheath 117. The device 100 can beloaded into a delivery sheath by several methods. One method is to loadthe device 100 on a delivery catheter 115 and to pull anchors 106straight and collapse cupped occlusive component 104 in the oppositedirection as the anchors, then insert the device and the deliverycatheter 115 into the delivery sheath 117 as shown in FIG. 7. Anothermethod is to load the device 100 on a delivery catheter 115, collapsethe cupped occlusive component 104 and to collapse or crush the anchors106 in the same direction as the cupped occlusive element 104, then loadthe device 100 on the delivery catheter 115 into a delivery sheath 117.Another method of delivery is to extend the cupped occlusive component104 along the delivery catheter 115 and fold or crush the anchors 106 asdescribed previously, then load the device 100 on the delivery catheter115 into the delivery sheath 117 as shown in FIG. 8. In someembodiments, the device is delivered over guidewire 119 using rapidexchange or other methods of over the guidewire delivery known to thoseof ordinary skill in the art (see, for example, U.S. Pat. Nos.5,040,548, 5,061,273 and 6,165,197 to Yock and U.S. Pat. No. 4,762,129to Bonzel). In some embodiments, when situated for delivery, the anchorsof the device 100 are positioned toward the distal end of the deliverycatheter 115 and both device and delivery catheter 115 are positionedwithin the delivery sheath 117 at the distal end of the sheath 117.

In some embodiments deployment of the devices can be achieved by pushingthe devices and the delivery catheter 115 out of the delivery sheath117, which is held in a constant location. In some embodiments, deliverycan be achieved by retracting the delivery sheath 117 while maintainingthe location of the device loaded on the delivery catheter 115. In someembodiments a combination of delivery catheter 115 push-out of theanchors 106 accompanied by delivery sheath 117 pull-back for cuppedocclusive element 104 deployment can be envisioned. In each of thesedeployment methods, the anchors 106 would deploy first, and then thecupped occlusive element 104 would be deployed and seated within theostium. Other methods of deployment can be envisioned by those skilledin the art. A keyed mandrel or delivery catheter can be used fordelivery. In such a configuration the lumen of the device can be shapedto match the shape of the mandrel or catheter to improve control ofdevice during deployment. The devices can be adapted for use withcommercially available pre-shaped, positionable, bendable, or steerabledelivery sheaths and/or catheters.

In some embodiments, the eyelet cap 212 is keyed such that anappropriately sized delivery catheter 115 (not shown) couples with theeyelet cap 212 at a keyed bore 213 (see FIG. 26). Alternative deploymentschemes would involve deploying the occlusive component within the leftatrium while keeping the anchors restrained. The device would then beadvanced until the cupped occlusive component apposes the ostium andthen the anchors would be deployed. This deployment scenario would usemethods described previously to load the device onto the deliverycatheter 115.

In some embodiments the device is configured to be repositionable orretrievable after delivery to the site of the ostium of the left atrialappendage. A retrieval cord can be looped from the proximal end of thedelivery catheter 115 through the lumen and through the proximal eyelet114 and back through the membrane component 109 to continue back towardsthe proximal end of the delivery catheter 115 where the cord may bemanipulated by an operator. Retrieval cords can be manufactured of anybiocompatible material of sufficient strength and size. Such materialsinclude fluoropolymers and expanded fluoropolymers and combinationsthereof, such as expanded polytetrafluoroethylene (ePTFE). The retrievalcord can be used to aid in the repositioning of the device when thedevice is partially deployed. This can be accomplished by gentletraction on both ends of the retrieval cord at its exit from theproximal end of the delivery catheter 115. The retrieval cord can alsobe used to retrieve the device when the device has been fully deployed.A fully deployed device is a device which has been deployed or detachedfrom the delivery catheter. The retrieval cord remains looped throughthe proximal eyelet 114 of the device during deployment and can be usedto pull the entire device back into the delivery sheath 117post-deployment, if necessary.

As shown in FIGS. 1 to 4 and in FIG. 6, a membrane component 109 isconfigured to inhibit passage of blood. Embodiments can provide amembrane component 109 configured to inhibit the passage of bloodthrough the membrane, i.e., substantially occludes the flow of bloodthrough the membrane. Some embodiments can provide a membrane component109 that is configured to induce rapid tissue ingrowth and immediatelyor rapidly occludes the passage of blood through the membrane. In someembodiments, the membrane component 109 provides for a blood or bodyfluid impermeable membrane that occludes the flow of blood or bodilyfluids through the membrane yet still promotes tissue ingrowth andendothelialization. Such embodiments can comprise a fluoropolymer suchas an expanded polytetrafluoroethylene polymer. In some embodiments theinhibition of blood or bodily fluid passage across the membranecomponent 109 is immediate and does not rely on the thrombotic process.Membrane component 109 can also serve as a tissue ingrowth scaffold fordurable occlusion and anchoring of the device. The microporous structureof the membrane component 109 can be tailored to promote tissue ingrowthand/or endothelialization. The membrane component 109 can be modified byvarious chemical or physical processes to enhance certain mechanical orphysical properties. A hydrophilic coating can be applied to membranecomponent 109 to promote its wettability and echo translucency.Additionally, a physiochemical modification can be employed whereby themembrane component 109 includes chemical moieties that promoteendothelial cell attachment, migration, and/or proliferation, or toresist thrombosis. A surface modified with covalently attached heparinis one non-limiting example of a membrane modification. In someembodiments the membrane is impregnated with one or more drug substancesthat are released in situ to improve healing response or reduce tissueinflammation. In some embodiments, the drug substance is selected fromthe group consisting of a corticosteroid, a human growth factor, ananti-mitotic agent, dexmethasone sodium phosphate, and anantithrombotic.

The membrane component 109 can be made of any biocompatible materials,including fluoropolymers such as polytetrafluoroethylene and expandedpolytetrafluoroethylene; polyesters; silicones; urethanes; or otherbiocompatible polymers and combinations thereof. Some embodimentscomprise a membrane component comprising a fluoropolymer such aspolytetrafluoroethylene or expanded polytetrafluoroethylene. In someembodiments, the membrane component comprises expandedpolytetrafluoroethylene.

Some embodiments of the hub component 110 of the invention areconstructed of a composite of nitinol wire and membrane. In someembodiments, the hub component 110 is constructed from wire. Theconstruction of the composite embodiment of the hub component isdetailed in a later example. Some embodiments of the device comprise alumen 122 extending along or parallel to the central axis of theexpandable frame. In some embodiments, the lumen can be sized to permitpassage of about an 0.9 mm diameter guide wire to facilitate coaxialalignment within a body cavity, such as the left atrial appendage. Thelumen passes through the proximal eyelet 114, the cupped occlusivecomponent 104, the hub component 110, the anchor component, and thedistal eyelet 113. A lumen 122 can be formed by winding wires around acenter pin 22 to form a hollow central core through each of thefollowing elements: proximal eyelet 114, the occlusive component 104,the hub component 110, the anchor component, and the distal eyelet 113.In some embodiments the lumen 122 permits fluoroscopic contrastinjection behind the seated device to facilitate acute seal assessment.

Some embodiments of the hub component 110 can be constructed of multiplenitinol wire components held together with fluoropolymers such asexpanded polytetrafluoroethylene (ePTFE) or various flexiblefluoroelastomers. In some embodiments a multi-component structure heldtogether with a flexible interposed element would permit articulationbetween the occlusion element and the anchoring element, thuspotentially facilitating a safer, more stable and effective occlusion.In some embodiments the hub component 110 can be constructed ofcontinuous wires, such as nitinol, with or without coverings.

In some embodiments one or more anchors 106 consist of multiple wiresthat radiate outward or radially while extending distally and containinga small turn or bend directed proximally at the end of the anchor. Insome embodiments the anchors 106 consist of looped wire (see FIGS. 1-4and 6) or individual wire radiations (see FIGS. 5B and 5C). In someembodiments, the proximal turn of the loops can be formed approximatelyperpendicular to the angle of the outward radiation of the one or moreanchors. In some embodiments one or more of the anchors 106 is bare. Insome embodiments one or more of the anchors 106 is covered in whole orin part by a membrane 108. In some embodiments anchors are notsubstantially covered with a membrane (see, for example, FIG. 8). Insome devices there are a combination of bare and covered/partiallymembrane covered anchors. In some embodiments membranes 108 of thelooped anchors 106 prevent the anchor legs from becoming entangledduring loading, deployment, retrieval and redeployment. In someembodiments, a membrane covering 108 is located around the proximal bendof the looped anchor 106. In some embodiments, the membrane covering 108can provide for rapid tissue ingrowth and device stabilization. In someembodiments paired wire anchors 106 with a looped end 107 provide adevice securing means that significantly reduces or prevents tissueperforation or piercing and the associated risk of pericardial effusion.In some embodiments the anchor element 106 with looped ends 107 iscapable of secure anchoring due to the radial expansion force from thewire elastic property and the terminating proximal turn's ability toengage or hook the left atrial appendage wall and trabeculae. The loopedend anchors 106 is likely capable of being recaptured and redeployedwith significantly reduced trauma or damage to the device or to thesurrounding tissue.

In some embodiments, anchors are NiTi wires. In some embodiments, theNiTi wires have a outer diameter from about 0.008″ to about 0.013″. Insome embodiments, the overall length of the anchor is from about 0.13″to about 0.63″. In some embodiments, the overall length of the proximalanchor turn is about 0.1″ to about 0.2″

In some embodiments, anchors, barbs, or portions of anchors and barbsare constructed of a non-permanent biodegradable or bioabsorbablematerial which are resorbed over a period of time. In some embodimentsthe bioabsorbable nature of the anchors and barbs allows active acutefixation, facilitates ingrowth, and reduces the risk of undesired tissueor organ perforation.

In some embodiments, anchors and/or barbs have one or more bends at ornear the connection point to the device. In some embodiments, the bendradius is between about 0.06″ to about 0.2″.

In some embodiments one or more of the anchors 106 is a single-wireanchor, i.e. non-looped wire, that radiates outward from the proximalcentral hub to a sharp point or atraumatic ball 145 on the terminatingend. In some embodiments, one or more of the single leg anchors containat least one dog-leg feature on the outward radiating wire element. Insome embodiments the dog-leg feature facilitates anchor disengagementwhen a sheath is passed over it for recapture. In some embodiments, thedistal end of an anchor having looped ends may be cut approximately atthe apex of the loop to form a pair of single wire anchors (see FIG.5C). In some embodiments, one or more anchors having looped ends have atleast one dog-leg feature (see FIG. 5A). In some embodiments, one ormore anchors have looped ends, and include two or more bends along thelength of the anchor (see, e.g., FIG. 5A). In some embodiments theplurality of distinct radiating wire anchoring elements give the devicean advantage because of the independence each anchoring element has fromthe other elements. Although not wishing to be bound by theory, it ispostulated that this independence allows the anchors 106 to conform tothe variable appendage anatomy while still maintaining secure anchoring.

In some embodiments, anchors include one or more hinge features. One ormore hinges may be at or adjacent to a point at which the anchorsconnect to the distal portion of the device, or along the longitudinallength of the anchor. In some embodiments, the hinges provide forrotation of the distal portion of an anchor of at least about 0-90degrees with respect to a proximal portion of the anchor. In someembodiments the hinge feature permits the anchors to better secure thedevice to the left atrial appendage.

Some embodiments have paired wire anchors 200 with a looped end 107formed such that the shaft of the wire anchors 202 have adjacent wiresthat are substantially in contact prior to diverging toward the loopedend 107 of the anchor. This configuration (shown in FIG. 23) would allowfor reduced deployment and repositioning forces. These embodiments couldalso reduce the likelihood of anchor crosstalk or entanglement whileloaded into a catheter prior to delivery. Some embodiments of loopedwire anchors include a rounded loop end, a diamond shaped loop end, apointed loop end, and a side by side loop end.

In some embodiments, the distance between the two legs of a looped wireanchor is greater at the base of the anchor than in a bend region of theanchor. In some embodiments a centerless grind process is employed toform the distance between the two legs of the anchor.

In some embodiments, the device 100 comprises two or more differentforms of anchors 106. For example, in some embodiments, the devicecomprises one or more looped wire anchors and one or more single-wireanchors.

In some embodiments, the conformation of an anchor pre-heat setting isdifferent from the conformation of the anchor post-heat setting.

In some embodiments, the anchor 106 further comprises at least one barb211 affixed to or wrapped around the anchor (see FIG. 25). In someembodiments, at least one barb is substantially perpendicular to theangle of the outward radiation of the respective anchor. In someembodiments, the barb protrudes in a direction away from the generaldirection of the anchor. In some embodiments the barb is a smaller gaugewire than that of anchor 106. In some embodiments, the barb contains atleast one dog-leg feature. In some embodiments, the barb terminates at asharp point at its distal end. In some embodiments the barb terminatesat its distal end as an atraumatic ball.

In some embodiments, the barb is fixed to or wrapped around the anchorat two or more points to form a loop. In some embodiments, the loopedbarbs include one or more (e.g., one, two, three, or more) bends,dog-legs, or hinges, or combinations of bends, dog-legs, and hinges.

It is understood that as the number of components on a device increases,it generally becomes progressively more difficult to deploy the devicein a catheter sheath of limited size. Additionally, as barbs aresometimes positioned so as to extend away from an anchor in a directionnot parallel to the longitudinal axis of the anchor, the barbs mightbecome entangled with other barbs, anchors or other device components.Accordingly, in some embodiments, barbs are constructed including a bendor a hinge, such that the barb/tine is bent backwards along the axis ofthe anchor while present in the anchor sheath but are outwardly deployedwhen the device moves out of the catheter sheath.

In some embodiments, a barb is positioned on a leading portion of theanchor, i.e. on a portion of the anchor closer to the distal end of thedevice than to the proximal end of the device. In some embodiments, thebarb located on the leading portion of the anchor is proximal-facingwhile in some embodiments, the barb located on the proximal end of thedevice faces the distal end of the device. In some embodiments, aproximal-facing barb is attached to a looped anchor while in someembodiments the proximal facing barb is attached to a single leg anchor.

Barbs can be designed so as to be compliant, non-compliant, or partiallycompliant and partially non-compliant. In some embodiments, some or allof a barb is covered or coated to prevent or limit tissue penetration.In some embodiments, the barb is covered or coated with suitablebiocompatible materials including, but not limited to, fluoropolymerssuch as polytetrafluoroethylene and expanded polytetrafluoroethylene;polyesters; silicones; urethanes; or other biocompatible polymers orcombinations thereof. In some embodiments, the coated- or covered-barbprovides a structure and substrate for tissue ingrowth around the barb.In some embodiments the coating or covering on the barb providesprotection against entanglement of adjacent anchors and/or barbs. Insome embodiments, barbs are coated/covered with a material whichminimizes friction against the catheter wall, thereby aiding deploymentand/or retrieval of the device. In some embodiments, a barb having oneor more sharp tips is coated/covered such that only limited tissuepenetration is permitted. In some embodiments, the covering of the barbis impregnated with one or more drug substances which are released insitu to improve healing response or reduce tissue inflammation. In someembodiments, the drug substance is selected from the group consisting ofa corticosteroid, a human growth factor, a anti-mitotic agent,dexmethasone sodium phosphate, and an antithrombotic.

In some embodiments, anchors 106 are formed from strands of twisted orbraided wires. In some embodiments barbs on such anchors are formed bycutting one or pulling away one or more strands of the twisted orbraided wire from the twisted or braided wire.

In some embodiments, the anchors and/or barbs include a textured surfaceto aid in securing the device to surrounding tissue.

In some embodiments, one or more anchors each includes two or morestructures selected from bends, dog-legs, hinges, barbs, and surfacetexturing.

In some embodiments the radial arrangement of the anchors is staggeredaccording to anchor feature (for example, by overall anchor length (e.g.long-short-long-short)). In some embodiments, the radial arrangement ofthe anchors is biased according to anchor feature (for example, byconfiguration (e.g. looped wire anchor-single leg anchor-looped wireanchor-single leg anchor)).

In some embodiments, anchors are spaced uniformly apart, i.e. eachanchor 106 is equally spaced radially about the circumference of thedistal portion of the device.

In some embodiments the anchor 106 exits the proximal central hub of thedevice at an angle substantially perpendicular to the longitudinal axisof the device. In some embodiments the anchor 106 exits the device at anangle between 20-80 degrees compared to the longitudinal axis of thedevice, wherein the distal point of the anchor extends to, andpotentially past, the distal eyelet.

In some embodiments, each of the one or more anchors is substantiallyidentical, i.e. each anchor has about the same overall length, the sameplanar arrangement (i.e. having similar absence or presence of one ormore dog-leg features; presence or absence of one or more hinges), thesame radial angle with respect to the longitudinal axis of the device(axis formed between distal and proximal end of the device), and thesame configuration (for example, a looped end anchor, a twisted wireend, or a single-wire anchor). In some embodiments, one or more of theanchors differs from at least one other anchor with respect to at leastone of overall length, planar arrangement, radial angle, orconfiguration.

Some embodiments as shown in FIG. 24 have single-leg anchors 204.Anchors 204 can be formed from the same wires that form the eyelet 144,in various embodiments. Anchor 204 comprises a shaft portion 206, arounded portion 208 and a wire end 210. The wire end 210 can beconfigured to twist or protrude away from the plane of rounded portion208 to serve as barbs or protrusions for further anchoring.

Some embodiments provide a looped wire anchor 106 with a barb 211attached to the anchor at multiple sites (shown in FIG. 25).

In some embodiments the anchor wires protrude from the device at a hubflange. In some embodiments, the hub flange is covered with a complianthub extension made as an overmold or as a pre-molded component.

An exemplary embodiment of the device is shown in FIG. 27A and includesa modular anchoring hub 217 that connects anchors 106 to the occludingdevice (including petals 112 supported by expandable frame 102) whereinanchors 106 are axially mounted into a flange 215 (shown in FIGS. 27Band 27B). Such a modular anchoring hub allows rapid customization of thetype of occluding device as well as the type and format of the anchorsand can allow optimization of the device based on selection criteriaincluding desired occlusive device, desired anchoring mechanism, andsize and anatomy of the left atrial appendage. In some embodiments, themodular anchoring component reduces the profile of the distal end of thedevice and therefore minimizes potential for thrombus formation.

In some embodiments, the modular anchoring component is attacheddirectly to the occlusion device or is attached to the occlusion devicevia a flexible connector. In some embodiments, the modular anchoringcomponent permits different arrangements of anchors. For example, insome embodiments the modular anchoring component permits the anchoringof single-leg type anchors, looped wire anchors, and combinations ofsingle-leg and looped wire anchors. In some embodiments, the axialattachment of the anchors to the modular anchoring component allows areduction in device profile and reduced deployment and retrieval forcesin the delivery catheter.

In some embodiments, the modular anchoring hub also allows for a varietyof anchor configurations (e.g. active or passive geometries, anchornumber, anchor size, anchor distribution and anchor length, and anchormounting to hub). In some embodiments, the legs of an looped wire anchorare adjacent to one another, i.e. in an adjacent configuration In someembodiments, legs of a first looped wire anchor are separated from oneanother by the leg of an adjacent looped wire anchor, i.e. in astaggered configuration Although not wishing to be bound by theory, itis thought that an adjacent configuration allows more side to sidemovement of the anchors while minimizing interference between adjacentanchors, and that a “staggered” configuration provides wider support atthe hub, minimizes side to side movement of the anchors, and due tointerference between adjacent anchors, provides further side to sidesupport.

In some embodiments, the device further comprises keyed eyelet caps toengage an appropriately keyed delivery catheter. In some embodiments thekeyed bore 213 accepts the end of a flattened delivery catheter. In someembodiments, suture holes 218 permit the passage of a looped suture fromthe catheter around the eyelet cap so as to secure the device to thecatheter. In some embodiments, the thread axis is offset from the eyeletaxis so as to reduce rotational torque to device generated duringrelease.

In some embodiments, eyelet caps comprise a sleeve and an end cap, eachmade of nitinol or other appropriate material. Sleeves are disposedaround the eyelet and, in some embodiments, are welded or adhered to theeyelet. In some embodiments, the sleeves includes one or more slotsradially arranged around the sleeves, each slot extending down thesleeve along the axis of the device. In some embodiments, the slotprovides access for welding and/or adhesive bonding. In someembodiments, the sleeves engage each of the frame wires and assist inmaintaining a desired spacing between the frame wires.

In some embodiments, the sleeves are added during device assembly, priorto bag attachment with the end cap added at the end of assembly. In someembodiments, the end cap is attached to the sleeve with a snap-inassembly wherein one or more tabs on the sleeve engage with a flange onthe end cap. In some embodiments the tabs and flange are aligned so asto confirm proper alignment and calibration between proximal and distaleyelets.

Some embodiments include an overmold of a suitable plastic material(e.g. thermoplastic or a fluoropolymer) over the sleeves. In someembodiments the overmold includes one or more lightly grooved areas forbag attachment.

In some embodiments, the device is optimized to have a particularocclusive disk diameter to device length ratio. In some embodiments theratio of occlusive disk diameter to the length of the device is between1:2 and 2:1. In some embodiments, the disk diameter to device lengthratio is 1:1. In some embodiments the waist length of the device (e.g.the distance between the distal aspect of the proximal occlusive diskand origination of the anchor projections) is adjusted so as to yieldthe desired ratio.

As shown in FIG. 9, some embodiments provide a membrane componentconfigured to inhibit passage of blood and an expandable frame formedfrom a plurality of wires having a cupped occlusive component with aflat proximal surface 116 and a cupped distal surface 118 at leastpartially covered with the membrane component 109, one or more anchors106 with looped ends 107 and a hub component 110. Such a configurationcan permit deeper, more secure seating within the left atrial appendageostium while still eliminating the residual left atrial appendage stumpthat could be a source of thrombus or blood clot formation.

Example 1

An about 1 meter length of 10% platinum drawn filled nitinol wire (FortWayne Metals, Fort Wayne, Ind.) with a diameter of about 0.23 mm isobtained. The specific length of the wire may or may not be measured,but the wire should be long enough to complete the winding pattern asdescribed in the following paragraph. The wire is obtained having beenelectropolished. Electropolishing nitinol wire imparts certain wellknown properties, such as spontaneously forming a titanium dioxide layeron the surface, selectively reducing the amount of nickel on the surfaceof the wire, and removing some of the stresses in the wire thusimproving fatigue.

A base jig 8 as described in FIG. 11 is obtained. A knot is tied intoone end of one length of an about 0.5 meter long wire and the unknottedend is fed through a wire feed hole 10. Two additional lengths of wire(about 1 meter each) are folded in half and the free ends are fedthrough the remaining four feed holes 12, 14, 16, 18, with the wireentering the holes at funnel-shaped opening 19 with the small feed holesat the bottom of opening 19. The wires then exit through holes 10, 12,14, 16 and 18 at the flat end surface of jig 8. Weights 20 are attachedto the free ends of the five wires to hold the wires taut and in place.The base jig is secured in a chuck of a lathe and center pin 22 isinserted into center pin hole 24 far enough to securely seat it.

The other end of center pin 22 is located inside the center hole 28 oftail stock support 26 which is chucked into the tail stock, wherein theclosed face 30 of the tail stock support 26 faces the base jig 8. Thebase jig 8 and tail stock support 26 are positioned about 5 cm apart. Awire guide 34 is used to prevent the wires from crossing. The base jig 8is positioned so that the wire feed holes 10, 12, 14, 16, 18 areoriented vertically above the center pin 22 and the wires are positionedon the trailing side of the center pin 22.

The petal jig hole 36 is rotated 720 degrees (deg.). The petal jig 38 isinserted into the petal jig hole 36. Without crossing the wires, thewires are placed on top of the petal jig 38. The base jig 8 is rotated360 deg to create the petals of the device. The base jig 8 is rotatedanother 720 deg with the wires placed on top of the center pin 22 inorder to create the center eyelet.

The anchor pin 40 is next inserted into the anchor pin hole 42. Thewires are then looped around the anchor pin 40 and the base jig isrotated 720 deg in order to form the distal eyelet. The wire pivot 7 isinserted into wire pivot hole 9. The wires are fed around the wire pivot7 and placed under anchor plate 11. The anchor plate 11 is secured withAllen head screws 14. The wires are cut on the weight 20 side of theanchor plate 11.

With the weights 20, the tail stock support 26, and the wire guide 34removed, the assembly can be placed in a convection oven set to 475 degC. for 14 minutes, for example. The assembly is removed from the ovenand quenched in water. The jigs are disassembled and the article isremoved.

The wire ends are trimmed to the eyelets and the petals are fanned inthe same direction as the helical winding, such that each petal isoriented 72 degrees offset relative to the adjacent petal. As aconsequence of the fanning of the petals, the anchor loops are alsofanned.

A heat set mandrel 44 is obtained as described in FIG. 12B. The articleis placed onto the heat set mandrel such that the cap 46 is positionedadjacent to the anchor loops. The article is then placed inside the heatset tool 48 (see FIGS. 12A and 12C) such that the petals are positionedinside a heat set tool and the anchor loops protruded over the lip ofthe heat set tool 48. Anchor loop pins 50 are inserted through theanchor loops and secured in the anchor pin holes 52. The heat setmandrel 44 is inserted onto the center hole of cross bar 54 (FIG. 12D)and the cross bar 54 is seated into the notches 56 of the heat set tool48. The heat set mandrel 44 is forced into the heat set tool 48 toachieve the desired angles of the anchors and the mandrel is then lockedin place using the set screw 58.

The assembly is placed in a convection oven set to 475 deg for 5 andtransferred to a 2 mm mandrel.

While maintaining the petal orientation, the article is powder coatedwith FEP powder (obtained from in house stock) in the following manner.A 2 mm outer diameter mandrel with a length sufficient to be insertedinto the blender described further in this paragraph is obtained. Themandrel 123 is flattened by crimping at two locations spaced about 2.5cm apart. See FIGS. 13 and 14. The mandrel 123 is inserted into thecenter hole of the article. One end of the mandrel 123 is grounded. Acommercial blender (Variable Speed Lab Blender, Waring, Torrington,Conn.) is obtained and a quantity of FEP powder is added, leaving thetip of the blender blades exposed. The article and mandrel are suspendedin the center of the blender, the lid is replaced, and the blender isturned on to the highest setting for about 5 seconds. The article andmandrel 123 are removed, the mandrel is tapped to achieve a more uniformpowder coating, and the article and mandrel 123 are then hung inside aconvection oven set to 320 deg C. for 3 minutes. The article and mandrel123 are removed from the oven, allowed to cool, and the mandrel isremoved. The excess FEP is cleaned from the mandrel, and the mandrel isreinserted into the article.

The article is extended in length on the mandrel 123 by grasping theproximal and center eyelets with tweezers. The eyelets are fixed inplace by positioning them beyond the crimps in the mandrel.

A porous ePTFE film having the following properties is obtained:

Methanol bubble point of 0.7 psi

Mass/area of 2.43 grams/square meter

Longitudinal matrix tensile strength of 96000 psi

Matrix tensile strength in the orthogonal direction of 1433 psi

Longitudinal maximum load of 1.6 kg/inch

Thickness of 0.00889 mm

Methanol bubble point is measured using a custom built machine with a 1inch diameter foot, a ramp rate of 0.2 psi/second and a liquid media ofmethanol. Length and width of the material are measured using a metalruler. Mass/area is measured using a balance (Model GF-400 Top LoaderBalance, ANG, San Jose Calif.) with a 36×5 inch sample. Longitudinalmaximum load is measured using a materials test machine (Model 5564,Instron, Grove City, Pa.) equipped with a 10 kg load cell. The gaugelength is 1 inch and the cross head speed is 25 mm/minute. Sample widthis 1 inch. Longitudinal tensile test measurements are taken in thelength direction of the material. Thickness is measured using athickness gauge (Mitutoyo Digital Indicator 547-400) with a footdiameter of % inch. The longitudinal matrix tensile strengths (MTS) arecalculated using the following equation:

${{Matrix}\mspace{14mu}{Tensile}\mspace{14mu}{Strength}} = \frac{\left( \sigma_{sample} \right)*\left( \rho_{PTFE} \right)}{\left( \rho_{sample} \right)}$where: ρ_(PTFE) = 2.2  grams/ccσ_(sample) = (Maximum  Load/Width)/Thicknessρ_(sample) = (Mass/Area)/ThicknessDensity is calculated using the formula, density=mass/volume.

A 30 mm film tube is constructed from the ePTFE material in thefollowing manner. For a 25 mm diameter device, a film with a slit widthof about 1.905 cm is wound on a 30 mm OD mandrel. The amount of filmoverlap is not critical but preferably there will be at least someoverlap of the edges. The tube is then removed from the mandrel andstretched to make the ID of the tube to be about 25 mm.

The film tube is slipped over the tensioned article and using ePTFEfilm, the ends of the tube are cinched around the two eyelets.

Another porous ePTFE film, having a layer of FEP, is obtained having thefollowing properties:

Mass/area of 36.1 grams/square meter

Maximum Load, Longitudinal of 12.6 kg/inch

Maximum Load, Transverse of 0.3 kg/inch

Thickness of 0.0012 inch

Test methods for the above tests are described previously. The FEPthickness in the film is about 62.5%. FEP thickness (%) is calculated asratio of the FEP thickness and the film thickness. The reported valuerepresents the average measurements for five samples. FEP thickness andfilm thickness is measured from scanning electron microscope images ofcross sections of the ePTFE/FEP laminate material in the followingmanner. The magnification is chosen to enable the viewing of the entirefilm thickness. Five lines perpendicular to the horizontal edge of theimage are randomly drawn across the full thickness of the film.Thickness is determined by measuring the thickness of the FEP and thethickness of the film.

A 2 mm wide strip of this FEP-coated ePTFE film, with the FEP side down,is wrapped four times around the cinched portions and heated with asoldering iron to bond the film layers together.

A tubular, porous expanded polytetrafluoroethylene tube having a 1.279mm ID and an 1.452 mm OD is obtained. It possessed the followingproperties:

Density of 0.531 g/cc

Matrix tensile strength in the longitudinal direction of 34215 MPa

Thickness of 0.086 mm.

About 4 mm lengths of this tube are placed over each anchor andpositioned as shown in FIGS. 1-3 and FIG. 7.

The article and mandrel are placed inside a convection oven set to 320deg C. for 3 minutes and then removed and allowed to cool. The excessePTFE material is trimmed.

Example 2

An article is constructed in the same manner, using the same materials,as Example 1 with the following exceptions. The film tube is not appliedas a tube, but rather it is slit longitudinally and the resulting flatsheet is used to cover the nitinol frame. Without tensioning theocclusive member, the sheet is draped over the top frame petals and theedges of the sheet are gathered and secured around the center eyelet.The occlusive component of the resulting article has a cupped occlusivecomponent with a flat proximal surface and a cupped distal surface asshown in FIG. 9.

Example 3

An article is constructed in the same manner, using the same materials,as Example 1 with the following exceptions. The cupped occlusive memberand the anchor component are detached from each other by clipping thecenter eyelet by hand. An ePTFE tube with a diameter similar to that ifthe outer diameter of the eyelet shown in FIGS. 19A-19B is procured andsecured to the distal eyelet of the cupped occlusive member and theproximal eyelet of the anchor component. The tube is secured byoverwrapping tape containing FEP as previously described.

Example 4

An article is constructed in the same manner, using the same materials,as Example 1 with the following exceptions. The cupped occlusive memberand the anchor component are detached from each other by clipping thecenter eyelet by hand. A ePTFE tube with a diameter similar to that ifthe outer diameter of the eyelet shown in FIGS. 19A-19B is procured andsecured to the distal eyelet of the cupped occlusive member and theproximal eyelet of the anchor component. The tube is secured by applyingLoctite 4011 adhesive to the outside diameter of each resulting eyeletand securing the ePTFE tube over the eyelets until cured.

Example 5

An article is constructed in the same manner, using the same materials,as Example 1 with the following exceptions. The cupped occlusive memberand the anchor component are detached from each other by clipping thecenter eyelet by hand. A ePTFE tube with a diameter similar to that ifthe outer diameter was formed from ePTFE film as described previously.The tube is secured to the distal eyelet of the cupped occlusive memberand the proximal eyelet of the anchor component. The assembly was thenheated at 320 degrees C. for 3 minutes allowing the tube to shrink andsecuring it to the eyelets.

In addition to being directed to the teachings described above andclaimed below, devices and/or methods having different combinations ofthe features described above and claimed below are contemplated. Assuch, the description is also directed to other devices and/or methodshaving any other possible combination of the dependent features claimedbelow.

Numerous characteristics and advantages have been set forth in thepreceding description, including various alternatives together withdetails of the structure and function of the devices and/or methods. Thedisclosure is intended as illustrative only and as such is not intendedto be exhaustive. It will be evident to those skilled in the art thatvarious modifications may be made, especially in matters of structure,materials, elements, components, shape, size and arrangement of partsincluding combinations within the principles described herein, to thefull extent indicated by the broad, general meaning of the terms inwhich the appended claims are expressed. To the extent that thesevarious modifications do not depart from the spirit and scope of theappended claims, they are intended to be encompassed therein.

What is claimed is:
 1. An occlusive device comprising: a membranecomponent configured to inhibit passage of blood; an expandable framehaving a distal end and a proximal end; a cupped occlusive componentfully covered by the membrane component; one or more anchors located ator near the distal end of said expandable frame; and a hub componentdisposed between, and connected to, said occlusive component and saidone or more anchors; wherein said expandable frame including saidanchors is formed from a plurality of wires extending from the proximalend to the distal end of said frame; wherein at least one of saidanchors includes a first leg and a second leg substantially parallel toeach other and wherein the first leg and the second leg converge at anend of the anchor to form a barbless loop; and wherein at least one ofsaid anchors is at least partially covered by a membrane covering.
 2. Anocclusive device according to claim 1, wherein said cupped occlusivecomponent has a first configuration upon application of tensile forceand a second configuration upon release of said tensile force, whereinsaid first configuration is a tube and said second configuration is acupped shape formed from at least two overlapping petals configured toallow movement between the at least two overlapping petals.
 3. Anocclusive device according to claim 1, wherein the membrane componentcomprises fluoropolymer.
 4. An occlusive device according to claim 3,wherein the membrane component comprises polytetrafluoroethylene.
 5. Anocclusive device according to claim 4, wherein the membrane componentcomprises expanded polytetrafluoroethylene.
 6. An occlusive deviceaccording to claim 1, wherein the plurality of wires comprise nitinol.7. An occlusive device according to claim 1, wherein at least one ofsaid anchors extends away from the device in a generally distaldirection and includes a first end in contact with the device and asecond end.
 8. An occlusive device according to claim 7, wherein the atleast one of said anchors is a single-leg anchor.
 9. An occlusive deviceaccording to claim 7, wherein the at least one of said anchors includesa bend near the second end of the anchor, and wherein the bend causesthe second end of the anchor to be generally proximal-facing.
 10. Anocclusive device according to claim 7, wherein the at least one of saidanchors includes a bend near the second end of the anchor, and whereinthe bend causes the second end of the anchor to be generallydistal-facing.
 11. An occlusive device according to claim 7, wherein theat least one of said anchors includes one or more dog-leg features. 12.An occlusive device according to claim 7, wherein the at least one ofsaid anchors includes one or more hinges.
 13. An occlusive deviceaccording to claim 1, wherein the one or more anchors includes aplurality of anchors uniformly disposed radially about the device. 14.An occlusive device according to claim 1, wherein the one or moreanchors includes a plurality of anchors disposed radially about thedevice such that adjacent anchors are substantially equally spaced fromone another for all pairs of adjacent anchors of the radially disposedplurality of anchors.
 15. An occlusive device according to claim 1,wherein the one or more anchors includes at least one single-leg anchorand at least one anchor having a first leg and a second leg, wherein thefirst leg and the second leg converge to form a loop.
 16. An occlusivedevice according to claim 1, wherein the one or more anchors comprises abioabsorbable material.
 17. An occlusive device according to claim 1,wherein the one or more anchors comprises a biodegradable material. 18.An occlusive device according to claim 1, wherein the one or moreanchors comprises a barb that includes a biodegradable or bioabsorbablematerial.
 19. An occlusive device according to claim 1, wherein themembrane component comprises a biodegradable or bioabsorbable material.20. An occlusive device according to claim 1, wherein the one or moreanchors are arranged about the device in a staggered arrangement.
 21. Anocclusive device according to claim 1, wherein said hub componentcouples the cupped occlusive component to the one or more anchors. 22.An occlusive device according to claim 1, further comprising a flexibleconnector that is attached at a first end of the flexible connector tothe cupped occlusive component and is attached at a second end of theflexible connector to the hub component, and wherein the one or moreanchors are attached to the hub component.
 23. An occlusive deviceaccording to claim 1, wherein the expandable frame includes an eyelet,and further comprising a cap component disposed over the eyelet, the capcomponent defining a bore configured to couple with a delivery catheter.24. An occlusive device according to claim 23, wherein the bore of thecap component is keyed to couple with a mating portion of a keyeddelivery catheter.
 25. An occlusive device comprising: a membranecomponent configured to inhibit passage of blood; an expandable framehaving a distal end and a proximal end; a cupped occlusive componenthaving a distal end and a proximal end; one or more anchors; and a hubcomponent configured as a flexible connector between said occlusivecomponent and said one or more anchors; wherein said cupped occlusivecomponent is fully covered by said membrane component and is formed froma plurality of wires extending from the proximal end of said cuppedocclusive component to the distal end of said cupped occlusivecomponent, and wherein at least one of said anchors includes a first legand a second leg substantially parallel to each other and wherein thefirst leg and the second leg converge at an end of the anchor to form abarbless loop; and wherein at least one of said anchors is at leastpartially covered by a membrane covering.
 26. An occlusive deviceaccording to claim 25, wherein said cupped occlusive component has afirst configuration upon application of tensile force and a secondconfiguration upon release of said tensile force, wherein said firstconfiguration is a tube and said second configuration is a cupped shapeformed from at least two overlapping petals configured to allow movementbetween the at least two overlapping petals.
 27. An occlusive deviceaccording to claim 25, wherein the membrane component comprisesfluoropolymer.
 28. An occlusive device according to claim 27, whereinthe membrane component comprises polytetrafluoroethylene.
 29. Anocclusive device according to claim 28, wherein the membrane componentcomprises expanded polytetrafluoroethylene.
 30. An occlusive deviceaccording to claim 25, wherein the plurality of wires comprise nitinol.31. An occlusive device according to claim 25, wherein said flexibleconnector is one or more wires formed into a spring.
 32. An occlusivedevice according to claim 25, wherein said flexible connector comprisesa beaded chain.
 33. An occlusive device according to claim 25, whereinsaid flexible connector comprises a coil type flexible connector.
 34. Anocclusive device according to claim 25, wherein said flexible connectorcomprises beads formed of braided wire.
 35. An occlusive deviceaccording to claim 25, wherein said flexible connector comprises aflexible tube.
 36. An occlusive device according to claim 35, whereinthe flexible tube comprises ePTFE.
 37. An occlusive device according toclaim 25, wherein said flexible connector comprises silicone.
 38. Anocclusive device according to claim 37, wherein the silicone includesreinforcing members.
 39. An occlusive device according to claim 25,wherein said flexible connector comprises a universal joint.
 40. Anocclusive device according to claim 25, wherein said flexible connectorcomprises a compressed spring.
 41. An occlusive device according toclaim 25, wherein at least one of said anchors extends away from thedevice in a generally distal direction and includes a first end attachedto the device and a second end.
 42. An occlusive device according toclaim 41, wherein the at least one of said anchors includes a bend nearthe second end, and wherein the bend causes the second end to begenerally proximal-facing.
 43. An occlusive device according to claim41, wherein the at least one of said anchors includes a bend near thesecond end, and wherein the bend causes the second end to be generallydistal-facing.
 44. An occlusive device according to claim 41, whereinthe at least one of said anchors includes one or more dog-leg features.45. An occlusive device according to claim 41, wherein the at least oneof said anchors includes one or more hinges.
 46. An occlusive deviceaccording to claim 25, wherein the one or more anchors includes aplurality of anchors uniformly disposed radially about the device. 47.An occlusive device according to claim 25, wherein the one or moreanchors includes a plurality of anchors disposed radially about thedevice such that adjacent anchors are substantially equally spaced fromone another for all pairs of adjacent anchors of the radially disposedplurality of anchors.
 48. An occlusive device according to claim 25,wherein the one or more anchors includes at least one single-leg anchorand at least one anchor having a first leg and a second leg, wherein thefirst leg and the second leg converge to form a loop.
 49. An occlusivedevice comprising: a membrane component configured to inhibit passage ofblood; an expandable frame having a distal end and a proximal end; acupped occlusive component having a first configuration upon applicationof tensile force and a second configuration upon release of said tensileforce; one or more anchors; and a hub component between said occlusivecomponent and said one or more anchors; wherein said cupped occlusivecomponent is fully covered by said membrane component; wherein saidfirst configuration of said cupped occlusive component is a tube andsaid second configuration is a cupped shape formed from at least twooverlapping petals configured to allow movement between the at least twooverlapping petals; wherein said expandable frame is formed from aplurality of wires extending from the proximal end to the distal end ofsaid frame, wherein at least one of said anchors includes a first legand a second leg substantially parallel to each other and wherein thefirst leg and the second leg converge at an end of the anchor to form abarbless loop; and wherein at least one of said anchors is at leastpartially covered by a membrane covering.
 50. An occlusive devicecomprising: a membrane component configured to inhibit passage of blood;an expandable frame having a distal end and a proximal end; a cuppedocclusive component having a first configuration upon application oftensile force and a second configuration upon release of said tensileforce; one or more anchors; and a flexible connector between saidocclusive component and said one or more anchors; wherein said cuppedocclusive component is fully covered by said membrane component; whereinsaid first configuration of said cupped occlusive component is a tubeand said second configuration is a cupped shape formed from at least twooverlapping petals configured to allow movement between the at least twooverlapping petals; and wherein said expandable frame is formed from aplurality of wires extending from the proximal end to the distal end ofsaid frame, wherein at least one of said anchors includes a first legand a second leg substantially parallel to each other and wherein thefirst leg and the second leg converge at an end of the anchor to form abarbless loop; and wherein at least one of said anchors is at leastpartially covered by a membrane covering.